Contributions
Abstract: P1187
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: Disease modifying therapy appears to be more effective in earlier stages of multiple sclerosis (MS) but its burden is not always justified. Biomarkers enabling identification of patients at higher risk for an early relapse or a more severe disease course can help with early treatment decisions. While MRI lesions and cerebrospinal fluid oligoclonal bands (CSF OCB) are known to predict relapses in patients with clinically isolated syndrome (CIS), prognostic relevance of novel CSF biomarkers has emerged recently.
Objective: We aimed to evaluate the predictive potential of CSF kappa free light chains (KFLC), neurofilament light chains (NFL) and chitinase-3-like 1 protein (CHI3L1) for relapses and disability progression in patients with CIS.
Methods: A real-life CIS cohort (n = 147, 106 females) with a median follow-up of 4 years was studied retrospectively. KFLC were measured by nephelometry and enzyme-linked immunosorbent assays were used for determination of CSF NFL and CHI3L1. A relapse and progression to EDSS ≥ 3 were set as outcomes in survival analyses.
Results: Sixty-seven patients had disease relapse and 28 reached EDSS ≥ 3. In 36% of our patients immunomodulatory treatment was initiated before the next relapse. The absence of OCB significantly decreased conversion to MS (HR = 0.239; 95% CI: 0.075-0.762; p = 0.016) but this association was not evident with absolute KFLC concentrations. CSF NFL levels were markedly higher in CIS patients with relapse within the first year compared to those who were stable (1094 ng/L vs. 588 ng/L). Every 100 ng/L increase of NFL predicted another relapse (HR =1.027, 95% CI: 1.008-1.045; p = 0.005) and a more pronounced effect in the first year after CIS diagnosis was observed. Every 10-ng/mL increase of CHI3L1 was associated with an earlier progression to moderate disability of MS (HR =1.04; 95% CI: 1.00-1.09; p = 0.052).
Conclusion: Our results further underline the prognostic relevance of CSF biomarkers in CIS. In addition to OCB higher CSF NFL are predictive for relapses, especially in the first year of the disease course. On the other hand, CSF CHI3L1 seems to be more associated with disability progression.
Disclosure: Andreja Emersic: nothing to disclose
Matej Perovnik: nothing to disclose
Nina Pislar: nothing to disclose
Klemen Pavlic: nothing to disclose
Maja Pohar Perme: nothing to disclose
Uros Rot received grants/research support from Biogen Idec and consultation fees/travel grants from Bayer, Biogen Idec, Genzyme, Merck-Serono, Novartis and Teva.
Support by the University Medical Centre Ljubljana research programme is acknowledged.
Abstract: P1187
Type: Poster Sessions
Abstract Category: Pathology and pathogenesis of MS - Biomarkers
Background: Disease modifying therapy appears to be more effective in earlier stages of multiple sclerosis (MS) but its burden is not always justified. Biomarkers enabling identification of patients at higher risk for an early relapse or a more severe disease course can help with early treatment decisions. While MRI lesions and cerebrospinal fluid oligoclonal bands (CSF OCB) are known to predict relapses in patients with clinically isolated syndrome (CIS), prognostic relevance of novel CSF biomarkers has emerged recently.
Objective: We aimed to evaluate the predictive potential of CSF kappa free light chains (KFLC), neurofilament light chains (NFL) and chitinase-3-like 1 protein (CHI3L1) for relapses and disability progression in patients with CIS.
Methods: A real-life CIS cohort (n = 147, 106 females) with a median follow-up of 4 years was studied retrospectively. KFLC were measured by nephelometry and enzyme-linked immunosorbent assays were used for determination of CSF NFL and CHI3L1. A relapse and progression to EDSS ≥ 3 were set as outcomes in survival analyses.
Results: Sixty-seven patients had disease relapse and 28 reached EDSS ≥ 3. In 36% of our patients immunomodulatory treatment was initiated before the next relapse. The absence of OCB significantly decreased conversion to MS (HR = 0.239; 95% CI: 0.075-0.762; p = 0.016) but this association was not evident with absolute KFLC concentrations. CSF NFL levels were markedly higher in CIS patients with relapse within the first year compared to those who were stable (1094 ng/L vs. 588 ng/L). Every 100 ng/L increase of NFL predicted another relapse (HR =1.027, 95% CI: 1.008-1.045; p = 0.005) and a more pronounced effect in the first year after CIS diagnosis was observed. Every 10-ng/mL increase of CHI3L1 was associated with an earlier progression to moderate disability of MS (HR =1.04; 95% CI: 1.00-1.09; p = 0.052).
Conclusion: Our results further underline the prognostic relevance of CSF biomarkers in CIS. In addition to OCB higher CSF NFL are predictive for relapses, especially in the first year of the disease course. On the other hand, CSF CHI3L1 seems to be more associated with disability progression.
Disclosure: Andreja Emersic: nothing to disclose
Matej Perovnik: nothing to disclose
Nina Pislar: nothing to disclose
Klemen Pavlic: nothing to disclose
Maja Pohar Perme: nothing to disclose
Uros Rot received grants/research support from Biogen Idec and consultation fees/travel grants from Bayer, Biogen Idec, Genzyme, Merck-Serono, Novartis and Teva.
Support by the University Medical Centre Ljubljana research programme is acknowledged.